Medicine for clogging blood vessels of eye fundus

ABSTRACT

An apparatus for clogging blood vessels of an eye fundus includes an illuminating optical system ( 1 ) for illuminating an eye fundus of a subject, who has been given an injection of an infrared fluorescent agent, with infrared rays of light and exciting the infrared fluorescent agent so as to generate infrared fluorescence, a photographic optical system ( 2 ) for observing and photographing the eye fundus, and a projecting optical system ( 21 ) for projecting a laser beam of light having a specific wavelength onto the subject who has been also given an injection of a photosensitive substance which undergoes a photochemical change by the laser beam. In the apparatus, while a region which emits infrared fluorescence is being observed, the laser beam is projected onto the photosensitive substance so as to clog blood vessels of a diseased part in the depth of the eye fundus.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a method, apparatus, and medicine for cloggingblood vessels of an eye fundus.

2. Description of the Prior Art

There is known a method for clogging blood vessels of an eye fundus.There is also known a photocoagulator used as an apparatus for cloggingblood vessels of an eye fundus. In the photocoagulator, an infraredfluorescent agent, called indocyaninegreen, is injected into a subject.When the infrared fluorescent agent circulates through the blood vesselsof the eye fundus of the subject, infrared rays of light for excitationare projected onto the eye fundus and, as a result, the infraredfluorescent agent is excited to emit fluorescence. While a regionemitting the fluorescence is being observed, a diseased part, such asneovascular vessels of a choroid, in the depth of the eye fundus isspecified. After that, a near-infrared semiconductor laser beam isprojected onto the diseased part so as to coagulate and treat thediseased part.

In this conventional method and apparatus, however, injury to normaltissues is unavoidable during the treatment because of photocoasulation.Therefore, it is expected to develop a fundus treating method by which adiseased part only is treated to the utmost without injury to normaltissues, and develop an apparatus and a medicine used for the treatment.

SUMMARY OF THE INVENTION

The present invention was made in view of the foregoing. It is thereforean object of the present invention to provide a fundus vessel cloggingmethod by which only a diseased part of an eye fundus is treated to theutmost without injuring normal tissues, an apparatus used for cloggingthe blood vessels, and a medicine to clog them.

In order to achieve the object, a fundus vessel clogging methodaccording to an aspect of the present invention includes the steps offurnishing a subject with a photosensitive substance which remains in adiseased part in the depth of the eye fundus where an infraredfluorescent agent remains and which undergoes a photosensitive change inthe diseased part by the use of a laser beam with a specific wavelengthas well as furnishing the subject with the infrared fluorescent agent,specifying the diseased part in accordance with emission of infraredfluorescence, and projecting the laser beam with the specific wavelengthonto the diseased part so that the photosensitive substance will producea photochemical change, thereby clogging blood vessels of the diseasedpart in the depth of the eye fundus.

In order to achieve the object, a fundus vessel clogging apparatusaccording to an aspect of the present invention includes an illuminatingoptical system for illuminating an eye fundus of a subject, who has beenfurnished with an infrared fluorescent agent, with infrared rays oflight so as to excite the infrared fluorescent agent and emit infraredfluorescence, a photographic optical system for observing andphotographing the eye fundus, and a projecting optical system forprojecting a laser beam with a specific wavelength onto the subject whohas been furnished with a photosensitive substance which undergoes aphotochemical change by means of the laser beam. In the apparatus, thelaser beam is projected onto the photosensitive substance and therebyblood vessels of the diseased part in the depth of the eye fundus areselectively clogged while a region emitting the infrared fluorescence isbeing observed.

In order to achieve the object, a medicine according to an aspect of thepresent invention includes a mixture containing an infrared fluorescentagent and a photosensitive substance of the following general formula(CHEMICAL FORMULA 3):{CHEMICAL FORMULA 3}

where n is 1 or 2.

In order to achieve the object, a medicine according to another aspectof the present invention includes a mixture containing an infraredfluorescent agent and a photosensitive substance of the followinggeneral formula (CHEMICAL FORMULA 4):{CHEMICAL FORMULA 4}

where n is 1 or 2.

A fundus vessel clogging apparatus according to another aspect of thepresent invention is characterized in that a diseased part in the depthof an eye fundus is specified by infrared fluorescence, and a laser beamwith a specific wavelength is projected onto a photosensitive substancewhich accumulates in the diseased part and undergoes a photochemicalchange by means of the laser beam for the purpose of treatment for thediseased part.

It is preferable to project an aiming laser beam which serves todistinguish a part where the laser beam is projected from a part wherethe infrared fluorescence emits in such a way as to superimpose theaiming laser beam upon the laser beam. More preferably, the aiming laserbeam is intermittently projected.

According to the present invention, the infrared fluorescent agent andthe photosensitive substance remain in the diseased part. In thissituation, the remaining of the photosensitive substance in the diseasedpart is larger than that of the infrared fluorescent agent therein.Therefore, the diseased part is observed and specified by the infraredfluorescent agent, and thereafter a laser beam with a wavelength bywhich the photosensitive substance produces a photochemical change isprojected. Thereby, since only the photosensitive substance produces aphotochemical change, an influence on normal tissues is avoided as muchas possible, and accordingly the diseased part only can be treated. Inthis case, if a mixture containing an infrared fluorescent agent and aphotosensitive substance is used as a medicine, intravenous injectioninto the subject can be given at a time.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic drawing showing optical systems of a fundus bloodvessel clogging apparatus according to a first embodiment of the presentinvention.

FIG. 2 is a schematic sectional view showing the tissue structure of aneye fundus according to the present invention.

FIG. 3 is a schematic drawing showing optical systems of a fundus bloodvessel clogging apparatus according to a second embodiment of thepresent invention.

FIG. 4 is a plan view showing a pattern plate of FIG. 3.

DETAILED DESCRIPTION OF THE EMBODIMENTS

FIG. 1 shows an embodiment of a method for clogging blood vessels of aneye fundus and an apparatus, which is applied to a fundus camera, forclogging the blood vessels. In FIG. 1, a reference numeral 1 designatesan illuminating optical system of the fundus camera, and referencenumeral 2 designates a photographic optical system thereof. Theilluminating optical system 1 includes a halogen lamp 3 and a xenon tube4. The halogen lamp 3 is conjugate to the xenon tube 4 with respect to acondenser lens 5. The illumination light of the halogen lamp 3 and thatof the xenon tube 4 are condensed by a condenser lens 6 and then areguided to a reflecting mirror 8 through an annular diaphragm 7. A laserdiode may be used instead of the halogen lamp 3.

The illumination light reflected by the reflecting mirror 8 passesthrough a relay lens 9, is then reflected by a perforated mirror 10, isguided to the eye fundus R of a subject through an objective lens 11,and illuminates the eye fundus R. The light beam from the eye fundus Rpasses through the objective lens 11 and is then guided to a focusinglens 13 through a hole 12 of the perforated mirror 10. A quick returnmirror 14 is disposed behind the focusing lens 13. When a photograph istaken with a film (i.e., when a still image is recorded), the quickreturn mirror 14 is removed from the optical path of the photographicoptical system 2. An image of the fundus is formed on a film 15 by thefocusing lens 13. On the other hand, during observation, the light beamfrom the fundus R is reflected by the quick return mirror 14, and thefundus image is formed on a CCD 16. A signal output of the CCD 16 isconverted into an image signal by an image processing circuit (notshown), and the fundus image is formed on a TV monitor (not shown). Asurgeon performs an operation, mentioned later, while observing the TVmonitor. In the case of visible fluorescence, a fundus image may beobserved by the use of a finder optical system 16′ which is made up of aquick return mirror 14′ and an eyepiece 15′. When the finder opticalsystem 16′ is not used, the quick return mirror 14′ is placed out of theoptical path of light reflected by the quick return mirror 14.

In accordance with a photographic mode, an exciter filter 17 for visiblefluorescence and an exciter filter 18 for infrared fluorescence areinserted into the optical path between the annular diaphragm 7 and thecondenser lens 6. Correspondingly to the insertion of the exciter filter17 for visible fluorescence and the exciter filter 18 for infraredfluorescence into the optical path of the illuminating optical system 1,a barrier filter 19 for visible fluorescence and a barrier filter 20 forinfrared fluorescence are inserted into the optical path between theperforated mirror 10 and the focusing lens 13 of the photographicoptical system 2. When the exciter filter 17 for visible fluorescence isinserted into the optical path of the illuminating optical system 1,green illumination light is guided to the fundus R, and the fundus R isilluminated with the green illumination light. On the other hand, whenthe exciter filter 11 for infrared fluorescence is inserted into theoptical path of the illuminating optical system 1, red and infraredillumination light is guided to the fundus R, and the fundus R isilluminated therewith. In a color photographic mode except thefluorescence photographic mode, the exciter filters 17, 18 are placedout of the optical path of the illuminating optical system 1, and thebarrier filters 19, 20 are placed out of the optical path of thephotographic optical system 2.

In the optical path of the illuminating optical system 1, there isdisposed a reflecting optical member 22 which serves as a constituentpart of a laser projection optical system 21 used for photocoagulationbetween the reflecting mirror B and the relay lens 9. In thisembodiment, a half mirror is used as the reflecting optical member 22.The laser projection optical system 21 includes a laser light source 23.Herein, a source for emitting a laser beam having a wavelength range ofvisible light (wavelength of 664 nm) is used as the laser light source23. A selective diaphragm 24 is disposed in front of the laser lightsource 23. The selective diaphragm 24 is conjugate to the fundus R withrespect to the objective lens 11. When a blood vessel clogging treatmentis conducted, a shutter 25 is inserted between the CCD 16 and the quickreturn mirror 14 in accordance with the power of a laser beam. Theshutter 25 has a function of preventing the CCD 16 from being burned bythe reflection of a laser beam having a high power. Likewise, a shutter25′ is inserted into the finder optical system 16′. The laser projectionoptical system 21 includes a light laser source 27 used for aiming. Thelaser light source 23 is conjugate to the laser light source 27 withrespect to a half mirror 28. Relay lenses 29, 30 are disposed betweenthe half mirror 28 and the reflecting optical member 22.

The selective diaphragm 24 consists of diaphragms 31, 32 which differ inaperture diameter from each other. Either of the selective diaphragms31, 32 is inserted between the relay lens 29 and the relay lens 30. Whena treatment for clogging blood vessels of a diseased part is conducted,a laser spot is formed on the fundus R in accordance with the diameterof an aperture of the selective diaphragm 24. A laser beam emitted bythe laser light source 27 is designed to have a wavelength range withinwhich the laser beam can pass through the barrier filter 20. In thisembodiment, the wavelength of the laser light source 27 is of a greenrange.

Since color photography and visible fluorescence photography are notdirectly relevant to the present invention, an explanation thereof isomitted. Thus, infrared fluorescence photography will be explained.

When the infrared fluorescence photography is carried out, an infraredfluorescent agent, called indocyaninegreen, of the following chemicalformula (CHEMICAL FORMULA 5) is injected into the veins of the subjector is taken by the subject in advance.{CHEMICAL FORMULA 5}

The infrared fluorescent agent circulates through the fundus and is thenilluminated with excitation light having a specific wavelength which haspassed through the exciter filter 18 for infrared fluorescence. Thereby,infrared fluorescence is emitted. If the fundus R has a diseased partK1, such as neovascular vessels, as shown in FIG. 2, the infraredfluorescent agent remains in the diseased part K1. Thereby, the amountof fluorescence from the diseased part K1 becomes larger than that offluorescence from around the diseased part K1. Therefore, the diseasedpart K1 shining brightly on a TV monitor can be located. Conventionally,an infrared laser beam has been projected, taking careful aim, onto thediseased part K1, and thereby the diseased part K1 has been coagulated.However, disadvantageously, this conventional photoagulation methodbrings about an injury to normal tissues therearound. In the presentinvention, therefore, a photosensitive substance of the followingconstitutional formula (CHEMICAL FORMULA 6) is injected into the veinsof the subject or is taken by the subject.{CHEMICAL FORMULA 6}

where n is 1 or 2.

This photosensitive substance is a tetrapyrrole derivative,Mono-L-aspartiru chlorin/e6/4 sodium salt Mono-L-aspartyl chlorin e6tetrasodium salt (Abbreviated Npe6), one of the tetrapyrrolederivatives, is accumulated together with the infrared fluorescent agentin the endothelium of blood vessels of the diseased part K1 such asneovascular vessels. Active oxygen is then generated by the projectionof a laser beam having the wavelength of 664 nm thereonto, and therebythe blood vessels of the diseased part K1 are clogged.

The following formula (CHEMICAL FORMULA 7) is a stereoisomer of CHEMICALFORMULA 6. It is preferable to use a chemical compound of this formulainstead of CHEMICAL FORMULA 6.{CHEMICAL FORMULA 7}

where n is 1 or 2.

The photosensitive substances are mixed with the infrared fluorescentagent, and advantageously a mixture containing them is given to thesubject by intravenous injection at a time.

As described above, the laser light source 23 emits a laser beam havingthe wavelength of 664 nm in order to cause the photosensitive substanceto generate a photochemical change. When the diseased part K1 istreated, a laser spot is formed on the fundus R in accordance with thediameter of an aperture of the selective diaphragm 24. The laser powerof the laser light source 23 can be regulated by a power regulator (notshown). It is desirable that the laser light source 23 is capable ofmaking the laser oscillation with the projection intensity of 20 to 500mW/cm² and with the full power of at least 500 mW.

In the laser projection optical system 21, a laser beam is projected byaiming at a marker which is a region of infrared fluorescence shiningbrightly in the fundus R. Thereby, the photosensitive substance iscaused to generate a photochemical change. Consequently, neovascularvessels can be clogged without injuring normal tissues to the utmost.

FIG. 3 shows a second embodiment of a fundus camera to which the presentinvention is applied. The fundus camera of the second embodiment isconstructed such that a pattern plate 33 is disposed between the laserlight source 27 for aiming and the half mirror 28, and the relay to theeye fundus R is made through relay lenses 34, 35. As shown in FIG. 4,for example, a star-shaped aiming pattern is projected onto the patternplate 33. Thereby, a distinction can be easily drawn between a partwhere the laser beam is projected and a part where infrared fluorescenceis emitted. In order to distinguish the two parts more easily, aconstruction may be employed in which the laser light source 27 foraiming is intermittently driven to flicker the aiming pattern.

According to the present invention, the method for clogging bloodvessels of an eye fundus and the apparatus and medicine used forclogging the blood vessels have the advantage that only the bloodvessels of a diseased part are clogged for a surgical treatment almostwithout injury to normal tissues.

1. A medicine including a mixture, the mixture comprising: an infraredfluorescent agent that remains in a diseased part in a depth of an eyefundus; and a photosensitive substance that remains in the diseased partin the depth of the eye fundus where said infrared fluorescent agentremains for clogging blood vessels at the diseased part by irradiating alaser beam with a specific wavelength to bring about a photochemicalchange at the diseased part, said photosensitive substance having thefollowing general formula:

where n is 1 or
 2. 2. A medicine including a mixture, the mixturecomprising: an infrared fluorescent agent that remains in a diseasedpart in a depth of an eye fundus; and a photosensitive substance thatremains in the diseased part in the depth of the eye fundus where saidinfrared fluorescent agent remains for clogging blood vessels at thediseased part by irradiating a laser beam with a specific wavelength tobring about a photochemical change at the diseased part, saidphotosensitive substance having the following general formula:

where n is 1 or 2.